Submissions for variant NM_001317778.2(SFTPC):c.42G>A (p.Pro14=)

gnomAD frequency: 0.00059  dbSNP: rs199905878

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000375927	SCV000472995	likely benign	Interstitial lung disease 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000281315	SCV000472996	likely benign	Surfactant metabolism dysfunction, pulmonary, 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002058716	SCV002403712	benign	not provided	2024-10-30	criteria provided, single submitter	clinical testing
Johns Hopkins Genomics, Johns Hopkins University	RCV000281315	SCV002570314	likely benign	Surfactant metabolism dysfunction, pulmonary, 2	2022-01-09	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002328879	SCV002626736	uncertain significance	Hereditary pulmonary alveolar proteinosis	2017-08-08	criteria provided, single submitter	clinical testing	The c.42G>A variant (also known as p.P14P), located in coding exon 1 of the SFTPC gene, results from a G to A substitution at nucleotide position 42. This nucleotide substitution does not change the at codon 14. However, this change occurs in the last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This variant was reported in a premature infant with respiratory distress syndrome; however, full gene sequencing of other genes related to surfactant deficiency was not performed (Lahti M et al. Eur. J. Hum. Genet., 2004 Apr;12:312-20). This vrariant was also identified in an individual with chronic obstructive pulmonary disease (Baekvad-Hansen M et al. Respir Med, 2010 Mar;104:418-25). This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Based on available evidence to date, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV002058716	SCV004032804	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	SFTPC: BP4, BP7