Submissions for variant NM_002386.4(MC1R):c.840del (p.Phe280fs)

dbSNP: rs2045705764

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	RCV001310272	SCV001468647	pathogenic	Skin/hair/eye pigmentation, variation in, 2	2020-12-15	criteria provided, single submitter	clinical testing	The c. 840delC variant is not present in publicly available population databases like 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC), Genome Aggregation Database (gnomAD) or in our in-house exome database. In-silico pathogenicity prediction programs like MutationTaster2 predicted this variant to be likely deleterious. The variant causes a frameshift at 280th amino acid position that creates stop codon at 313th amino acid position of the altered transcript. This may either cause a nonsense mediated decay of the mRNA resulting in no protein or a truncated protein due to premature stop codon.
Neuberg Centre For Genomic Medicine, NCGM	RCV001310272	SCV004047530	likely pathogenic	Skin/hair/eye pigmentation, variation in, 2		criteria provided, single submitter	clinical testing	The c.840del (p.Phe280LeufsTer34) missense variant in MC1R gene has been submitted to ClinVar as a Pathogenic variant, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Phe280LeufsTer34 variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant causes a frameshift starting with codon Phenylalanine 280, changes this amino acid to Leucine residue, and creates a premature Stop codon at position 34 of the new reading frame, denoted p.Phe280LeufsTer34. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.