Submissions for variant NM_002471.4(MYH6):c.735+16C>T

gnomAD frequency: 0.00093  dbSNP: rs76202841

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000612074	SCV000719691	benign	not specified	2017-06-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000612074	SCV001442717	benign	not specified	2020-10-26	criteria provided, single submitter	clinical testing	Variant summary: MYH6 c.735+16C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0024 in 251488 control chromosomes in the gnomAD database, including 6 homozygotes. The observed variant frequency is approximately 94- fold the estimated maximal expected allele frequency for a pathogenic variant in MYH6 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.735+16C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001727769	SCV001471713	benign	not provided	2021-09-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002063286	SCV002408815	benign	Hypertrophic cardiomyopathy 14	2025-01-23	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000612074	SCV001924345	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000612074	SCV001926344	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001727769	SCV001975560	likely benign	not provided		no assertion criteria provided	clinical testing